Increased glomerular size occurs in the presence of normal maturation, following unilateral nephrectomy in humans and animals, and in disease states such as diabetes mellitus. The hormonal regulation of compensatory hypertrophy is not fully understood, however total kidney IGF-I mRNA levels are increased following unilateral nephrectomy. This suggests a role for this hormone in hypertrophy of the adult kidney as well as in normal development. There are abnormalities in the circulating levels of GH in some diseases associated with increases in glomerular extracellular matrix and cell number, such as diabetes mellitus. The availability of transgenic mouse strains expressing elevated levels of IGF-I, GH, and GHRF provides an opportunity to study the renal effects of chronic hormone exposure. We have observed that mice containing an MT-I IGF-I fusion gene develop large glomeruli which are normal in appearance, whereas those transgenic for either growth hormone or growth hormone releasing factor have large glomeruli which are hypercellular. In addition, progressive glomerulosclerosis develops in the GH and GHRF transgenic mice. We further showed that there was an upregulation of mRNA for extracellular matrix components in the kidneys of the GH animals, which persisted late in the course of the disease. Surprisingly, proliferation also persists at late stages, when glomerular scarring was essentially endstage.